Elifcan TAŞDELEN, Lütfi DOĞAN
Acta Haematologica Oncologica Turcica - 2026;59(2):180-186
Aim: Familial adenomatous polyposis (FAP) is the most common hereditary adenomatous polyposis syndrome caused by pathogenic variants in the APC gene. This study aimed to describe the clinical and molecular characteristics of four unrelated patients harboring previously unreported APC variants. Methods: Four unrelated patients referred for suspected hereditary cancer predisposition were included in the study. Genomic deoxyribonucleic acid extracted from peripheral blood samples was analyzed using a hereditary cancer syndrome multigene panel via next-generation sequencing. Results: Four previously unreported heterozygous APC variants were identified: NM_000038.6:c.1621del (p.Gln541SerfsTer8), c.2194_2195del (p.Asn732Ter), c.3804_3808del (p.Ile1269PhefsTer5), and c.4066_4067dup (p.Gly1357GlnfsTer59). All variants were predicted to be loss-of-function and were expected to result in premature protein truncation. Only one variant was located within the mutation cluster region (MCR), whereas the remaining three were identified outside the MCR in patients with classical FAP. Conclusion: This case series expands the molecular spectrum of APC-associated polyposis by describing four previously unreported protein-truncating variants. Our findings further illustrate the clinical heterogeneity associated with APC-related disorders and underscore the value of comprehensive molecular characterization in individuals with suspected hereditary cancer predisposition.
